Document Type : Review Article

Authors

Men’s Health and Reproductive Health Research Centre, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Abstract

Background & Objective: Urothelial carcinoma is the seventh most common cancer in the world. The histological classification of papillary carcinoma is one of the most important determinants for its prognosis. Sometimes there is an overlap in the extent of the tumor, and the accurate microscopic diagnosis of the tumor is not always easy. The aim of this study was to evaluate P53 and CK20 immunohistochemical markers in comparison with morphologic findings in low- and high-grade urothelial carcinomas.
Methods: For this descriptive study, urinary bladder samples were collected from 50 cancer patients who had undergone biopsy and surgery in Shohaday-e Tajrish Hospital of Tehran, Iran, during the years 2015-2016. P53 and CK20 were studied, and the demographic and histopathological characteristics of the tumor were also analysed.
Results: The mean age of patients enrolled in this study (48 males and 2 females) was 65.8±11.9. Twenty-five cases presented with low-grade and 25 cases presented with high-grade papillary urothelial carcinomas. Sensitivity, specificity, and positive and negative predictive values for P53 were 48%, 80%, 70.5%, and 60.6%, respectively, while the same values for CK20 were 44%, 92%, 84.6%, and 62.2%, respectively. Immunohistochemical results were also positively correlated with the extent of the tumor.
Conclusion: Based on the results, P53 and CK20 may serve as specific markers for diagnosis of low- and high-grade papillary urothelial carcinoma but not sensitive. P53 and ck20 staining have also a high specificity as 80% and 92% and low sensitivity compared to the low and high morphology of papillary carcinoma, thus their positive and their staining intensity are valuable for diagnosis, but their negative results are not determinant.

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Main Subjects

  1. Bertz S, Otto W, Denzinger S, Wieland WF, Burger M, Stöhr R, et al. Combination of CK20 and Ki-67 immunostaining analysis predicts recurrence, progression, and cancer-specific survival in pT1 urothelial bladder cancer. Europ Urol. 2014;65(1):218-26. [DOI:10.1016/j.eururo.2012.05.033] [PMID]
  2. Kolahdoozan Sh, Sadjadi A, Radmard AR, Khademi H. Five Common Cancers in Iran. Arch Iran Med. 2010;13(2):143-6.
  3. Hodges KB, Lopez-Beltran A, Davidson DD, Montironi R, Cheng L. Urothelial dysplasia and other flat lesions of the urinary bladder: clinicopathologic and molecular features. Human Pathol. 2010;41:155-62. [DOI:10.1016/j.humpath.2009.07.002] [PMID]
  4. Ohsawa I, Nishimura T, Kondo Y, Kimura G, Satoh M, Matsuzawa I, et al. Detection of urine survivin in 40 patients with bladder cancer. J Nippon Med Sch. 2004;71(6):379-83. [DOI:10.1272/jnms.71.379] [PMID]
  5. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424. [DOI:10.3322/caac.21492] [PMID]
  6. Antoni S, Ferlay J, Soerjomataram I, Znaor A, Jemal A, Bray F. Bladder cancer incidence and mortality: a global overview and recent trends. European urology. 2017;71(1):96-108. [DOI:10.1016/j.eururo.2016.06.010] [PMID]
  7. Asgari M, Maybodi MN, Abolhasani M. Differential diagnosis of urothelial carcinoma in situ from non-neoplastic urothelia: Analysis of CK20, CD44, P53 and Ki67. Med J Islam Repub Iran. 2016;30:400.
  8. Rajcani J, Kajo K, Adamkov M, Moravekova E, Lauko L, Felcanova D, et al. Immunohistochemical characterization of urothelial carcinoma. Bratislavske Lekarske Listy. 2013;114(8):431-8. [DOI:10.4149/BLL_2013_091] [PMID]
  9. Khayamzadeh M, Aliakbari F, Zolghadr Z, Emadeddin M, Ahadi M, Akbari ME, Abedi AR, Nematollahi Sh, Hosseini SJ. Five-year Survival Rate of Bladder Cancer in Iran during 2001-2007. Iran J Pathol, 2020.118375.2287 [DOI:10.30699/ijp.2020.118375.2287] [PMID] [PMCID]
  10. Mai KT, Flood TA, Williams P, Kos Z, Belanger EC. Mixed low-and high-grade papillary urothelial carcinoma: histopathogenetic and clinical significance. VirchowsArchiv. 2013;463(4):575-81. [DOI:10.1007/s00428-013-1456-7] [PMID]
  11. Shariat SF, Ashfaq R, Karakiewicz PI, Saeedi O, Sagalowsky AI, Lotan Y. Survivin expression is associated with bladder cancer presence, stage, progression, and mortality. Cancer: Interdisciplin Int J Am Cancer Soc. 2007;109(6):1106-13. [DOI:10.1002/cncr.22521] [PMID]
  12. Mumtaz S, Hashmi AA, Hasan SH, Edhi MM, Khan M. Diagnostic utility of p53 and CK20 immunohistochemical expression grading urothelial malignancies. Int Arch Med. 2014;7(1):36. [DOI:10.1186/1755-7682-7-36] [PMID] [PMCID]
  13. Hasan IA, Gaidan HA, Al-kaabi MM. Diagnostic value of immunohistochemical panel (Cytokeratin CK 7, Cytokeratin CK20, High molecular weight cytokeratin HMWCK (clone CK34βE12) and Prostatic specific antigen (PSA) in differentiation between poorly differentiated prostatic and urothelial carcinoma. Iraq J Cancer Med Gen. 2018;11(1):7-13.
  14. Weyerer V, Schneckenpointner R, Filbeck T, Burger M, Hofstaedter F, Wild PJ, et al. Immunohistochemical and molecular characterizations in urothelial carcinoma of bladder in patients less than 45 years. J Cancer. 2017;8(3):323. [DOI:10.7150/jca.17482] [PMID] [PMCID]
  15. Buolamwini JK & et al.: Small molecule antagonists of the MDM2 oncoprotein as anticancer agents. Curr Cancer Drug Target. 2005, Feb;5(1 ):57-68 [DOI:10.2174/1568009053332672] [PMID]
  16. McKenney J, Desai S, Cohen C, Amin MB. Discriminatory Immunohistochemical Staining ofUrothelial Carcinoma in Situ and Non-neoplastic Urothelium. Am J Surg Pathol. 2001;25(8):1074-8. [DOI:10.1097/00000478-200108000-00013] [PMID]
  17. Cumberbatch MGK, Noon AP. Epidemiology, aetiology and screening of bladder cancer. Transl Androl Urol. 2019;8(1):5-11. [DOI:10.21037/tau.2018.09.11] [PMID] [PMCID]
  18. Yang Y, Kaimakliotis HZ, Williamson SR, Koch MO, Huang K, Barboza MP, et al., editors. Micropapillaryurothelial carcinoma of urinary bladder displays immunophenotypic features of luminal and p53-like subtypes and is not a variant of adenocarcinoma. Urol Oncol: Seminars and Original Investigations; 2019: Elsevier. [DOI:10.1016/j.urolonc.2019.10.013] [PMID]
  19. Korkolopoulou P: The role of p53, mdm2, and b-2 oncoproteins, epidermal growth factor receptor and prolifration markers in the prognosis of urinary bladder cancer. Patol Res Pract 1997,193(11 -12):767-75 [DOI:10.1016/S0344-0338(97)80055-6]
  20. Das D, Dey RK, Saha S, Das TK. Utility of a dual immunostain like p53 and CK20 to aid in the diagnosis and categorization of neoplastic bladder biopsies. J Evol Med Den Sci-JEMDS. 2015;4(25):4261-9. [DOI:10.14260/jemds/2015/616]
  21. Barth I, Schneider U, Grimm T, Karl A, Horst D, Gaisa NT, et al. Progression of urothelial carcinoma in situ of the urinary bladder: a switch from luminal to basal phenotype and related therapeutic implications. Virchows Archiv. 2018;472(5):749-58. [DOI:10.1007/s00428-018-2354-9] [PMID] [PMCID]
  22. Humphrey PA, Moch H, Cubilla AL, Ulbright TM, Reuter VE. The 2016 WHO classification of tumours of the urinary system and male genital organs-part B: prostate and bladder tumours. Eur Urol. 2016;70(1):106-19. [DOI:10.1016/j.eururo.2016.02.028] [PMID]
  23. Chou R, Gore JL, Buckley D, Fu R, Gustafson K, Griffin JC, et al. Urinary Biomarkers for Diagnosis of Bladder Cancer: A Systematic Review and Meta-analysis. Ann Intern Med. 2015;163(12):922-31. [DOI:10.7326/M15-0997] [PMID]
  24. Koletsas N, Koletsa T, Choidas S, Anagnostopoulos K, Touloupidis S, Zaramboukas T, et al. Immunohistochemical Investigation of HER/AKT/mTOR Pathway and Cellular Adhesion Molecules in Urothelial Carcinomas. Patholog Res Int. 2017:6794150. [DOI:10.1155/2017/6794150] [PMID] [PMCID]
  25. EL-RASHIDY M, AYA S. Immunohistochemical Study of the Role of CK20, p53 and Ki-67 in Differentiation of Some Urothelial Lesions and Urothelial Carcinoma of the Urinary Bladder. Med J Cairo Uni. 2018;86(September):2687-95. [DOI:10.21608/mjcu.2018.59607]
  26. Sanli O, Dobruch J, Knowles MA, Burger M, Alemozaffar M, Nielsen ME, et al. Bladder cancer. Nature reviews Dis primers. 2017;3(1):1-19. [DOI:10.1038/nrdp.2017.22] [PMID]
  27. Yikilmaz TN, Dirim A, Ayva ES, Ozdemir H, Ozkardes H. Clinical use of tumor markers for the detection and prognosis of bladder carcinoma: A comparison of CD44, cytokeratin 20 and survivin. Urol J. 2016;13(3):2677-83.
  28. Kamat AM, Hahn NM, Efstathiou JA, Lerner SP, Malmström PU, Choi W, et al. Bladder cancer. The Lancet. 2016;388(10061):2796-810. [DOI:10.1016/S0140-6736(16)30512-8]
  29. Uchida t: Clinical significance of p53, mdm2 and bci2 expression in transitional cell carcinoma of bladder. Oncol Rep, 2002, marapr,9(2),253-9. [DOI:10.3892/or.9.2.253]
  30. Hashimoto h: Role of p53 and mdm2 in tumor proliferation and determination of the prognosis of TCC of renal pelvises and ureter. Int J Urol 2000, Dec, 7(12),457-63. [DOI:10.1046/j.1442-2042.2000.00230.x] [PMID]
  31. Toll AD, Epstein JI. Invasive low-grade papillary urothelial carcinoma: a clinicopathologic analysis of 41 cases. The American journal of surgical pathology. 2012;36(7):1081-6. [DOI:10.1097/PAS.0b013e318253d6e0] [PMID]
  32. Roychowdhury A, Dey R, Bandyapadhyay A, Bhattacharya P, Mitra R, Dutta R. Study of mutated p53 protein by immunohistochemistry in urothelial neoplasm of urinary bladder. J Indian Med Assoc. 2012;110(6):393-6.
  33. Anadi RC, Dey RK. Expression of p53 Protein by Immunohistochemistry in Urothelial Neoplasm: A Hospital-based Study from Eastern India.
  34. Shim J-W, Cho KS, Choi Y-D, Park Y-W, Lee D-W, Han W-S, et al. Diagnostic algorithm for papillary urothelial tumors in the urinary bladder. Virchows Archiv. 2008;452(4):353-62. [DOI:10.1007/s00428-008-0585-x] [PMID] [PMCID]
  35. Moradi Tabrizi H, Nazar E, Ahmadi SA, Azimi E, Majidi F. Survivin and Her2 Expressions in Different Grades of Urothelial Neoplasms of Urinary Bladder. Iran J Pathol. 2021; 16(2): 154-161 [DOI:10.30699/ijp.2020.130859.2447] [PMID] [PMCID]
  36. Jalali Nadoushan MR, Ghorbanian E, Taheri T. Relationship between grade and MDM2 oncoprotein overexpression in transitional cell carcinoma of the urinary bladder. Iran J Pathol, (2006)1, (1), 17-20